After almost a century of accumulating evidence that drug addiction makes humans prone to opportunistic infections, it is still not known definitively which mechanisms are responsible for this susceptibility. The addiction milieu, including poor nutrition and dirty needles, and both indirect and direct effects of the opiates on the immune system have been positively implicated as part of this phenomenon. However little is actually proven as to the relative contributions of each of these factors. In particular, the mechanism(s) by which opiates directly modulate human immunity are at best obscure. The recent discovery of an inducible morphine receptor on mitogen activated T lymphocytes and the lack of such a receptor on nonactivated human peripheral lymphocytes provides a starting point for investigating the direct opiate effects. Three goals for such research would include: l. studies to define the specific cell population(s) containing the inducible morphine binding site and to establish the pharmacological specificity of the site; 2. an attempt to clone the morphine binding site by comparing mRNA pools in the activated and nonactivated cells using subtractive techniques in an attempt to identify the mRNA for this site; and 3. investigations of the processes by which the cells lacking morphine binding sites respond to opiates. In this latter case, it has been found that morphine can be taken up by the cells at which point the morphine can then bind to internal subcellular fractions, e.g., the microsomes, and presumptively affect the internal metabolism of the cell. With the rise of such opportunistic diseases as AIDS and antibiotic resistent tuberculosis, it becomes important to fully understand the mechanisms by which opiates and other drugs of abuse (cocaine) compromise the immune system. Clearly different chemical interventions are needed for receptor based mechanisms and those involving uptake and internalization.